Antineoplastic drugs have serious effects on patients. Methods for reducing these toxic side effects without simultaneously diminishing lethality to cancer cells should clinically be very useful. Certain drugs, including streptovitacin A and caffeine, prevent killing of BHK (normal) cells by antineoplastic agents, including cytosine arabinoside, in vitro. But polyoma virus-transformed BHK cells (malignant) are still killed. We propose to extend our in vitro findings to mice, to learn whether we can similarly protect critical normal tissues such as bone marrow and intestinal epithelium against antineoplastic agents. We propose to treat mice with protective and antineoplastic drugs alone and in combinations under different time schedules. We will examine gross properties of mice such as survival, weight, and cell properties such as cell number and kinetics of thymidine incorporation. We hope to find combinations of drugs that will allow higher doses of antineoplastic agents to be used with less serious side effects. We also are planning in vitro screening for additional protective drugs. Success with these mouse experiments should lead to clinical trials, in cooperation with chemotherapists at the Sidney Farber Cancer Institute.